1. Field of the Invention
The present invention relates to a method for the production of a compound of interest by microbial fermentation, wherein the microbial host cell used has been modified in its genome such that it results in a deficiency in the production of at least one non-ribosomal peptide synthase. The present invention further relates to a microbial host cell that has been modified in its genome such that it results in a deficiency in the production of at least one non-ribosomal peptide synthase. The invention further relates to a compound of interest.
2. Description of Related Art
An ever increasing number of compounds is produced by microbial fermentation at industrial scale. Such compounds of interest range from primary and secondary metabolites, such as e.g. citric acid and antibiotics, respectively, to proteins, enzymes and even complete microorganisms, e.g. in the form of baker's yeast or biomass.
At microbial fermentation on industrial scale several problems may occur that ultimately result in reduction of the yield of the compound of interest and/or increase the cost price of the compound of interest. The problems may e.g. relate to viscosity of the broth during fermentation, oxygen transfer during fermentation or formation of unwanted by-products such as oxalate. A problem encountered in microbial fermentations with the use of certain host systems such as fungi is the production of toxic products such as mycotoxins. WO00/39322 describes the provision of an Aspergillus mutant which is deficient in the production of toxins and its use in a process to produce a polypeptide of interest. Other problems inter alia encountered in microbial fermentations are hampered filtration of the product during down stream processing and coating of the fermentation devices due to unwanted insoluble by-products produced by the microbial cell during the fermentation.
To reduce problems during fermentation, the fermentation and downstream processing conditions for a specific product can be optimized. However, this optimization per product does not allow standardisation of fermentation and down stream processing protocols. When typically a large number of different products is produced within one facility, standardization of fermentation and down stream processing protocols results in a substantially more efficient use of the facility and thus more efficient production.
There is thus still a need for an improved method for the production of a compound of interest by microbial fermentation which allows standardised fermentation protocols and improved down stream processing.